1. Field of the Invention
This invention relates to a system, method and probe for use in measuring hydrogen ion concentrations, or pH, in a sample medium and, more particularly, to a minimally invasive, micro-sized pH probe having a pH-sensitive electrode, a reference electrode and a temperature electrode arranged within a probe housing. Preferably, a size of the probe housing minimizes the amount of trauma introduced by insertion of the pH probe into physiological tissues, muscles, or fluids.
2. Description of the Related Art
The following descriptions and examples are not admitted to be prior art by virtue of their inclusion within this section.
Generally speaking, pH is a measure of the hydrogen ion (H+) concentration within an aqueous solution. More specifically, pH is an indication of the acidity or alkalinity of a solution, and is defined as the negative logarithm of the H+ concentration. A solution having a pH value of 7.0 is typically considered a neutral solution, whereas lower pH values (i.e., higher H+ concentrations) indicate acidic solutions and higher pH values (i.e., lower H+ concentrations) indicate basic or alkaline solutions. In this manner, the acidity or alkalinity of a solution may be measured on a pH scale of about −2 to about 16. For each pH unit above 7.0, the H+ concentration is decreased tenfold, and vice versa.
In physiological solutions, maintenance of proper pH levels is critical, due to the pH dependency of chemical reactions that occur in the body. For example, all cells in the body continually exchange chemicals (e.g., nutrients, waste products, and ions) with interstitial fluids, which in turn, exchange chemicals with plasma in the bloodstream. A dominant mode of exchange between these fluids (i.e., intracellular fluid, interstitial fluid, and blood plasma) is diffusion through membrane channels, due to a concentration gradient associated with the chemical composition (and thus the pH) of these fluids. In order to maintain proper pH levels inside the cells, pH levels outside the cells must be kept relatively constant. This constancy is known in biology as H+ homeostasis.
Cellular health begins to decline when H+ homeostasis between the intracellular fluid, interstitial fluid and blood plasma is not maintained. As an example, the normal pH of (arterial) blood plasma, otherwise referred to as “physiological pH,” is about 7.4. If, for instance, pH levels of the blood plasma and interstitial fluid are too low (i.e., less than about 7.35), an excess of hydrogen ions will enter the cell, thereby increasing the acidity of the intracellular fluid and creating a condition called “acidosis.” Examples of conditions that cause physiological pH to drop may include hypoxia due to, for example, hypoventilation (e.g., caused by lung and airway disorders), low cardiac output (e.g., during shock states and myocardial infarction), and blood defects (e.g., sepsis, anemia and CO poisoning); inhalation or increased production of CO2; and accumulation of organic or inorganic acids (e.g., lactic acid, hydrochloric acid and carbonic acid). Extreme acidosis occurs in the cells when physiological pH drops to approximately 7.0.
If, on the other hand, pH levels of the blood plasma and interstitial fluid are too high (i.e., greater than about 7.45), an excess of hydrogen ions will leave the cell, thereby increasing the alkalinity of the intracellular fluid and creating a condition called “alkalosis.” Examples of conditions that cause physiological pH to rise may include hyperventilation, fever, some types of central nervous system damage, and loss of potassium (K+), sodium (Na+) and hydrochloric acid (HCl) due to pyloric obstruction, prolonged vomiting or diuretic alkalosis. Extreme alkalosis occurs in the cells when physiological pH increases to approximately 7.7.
As such, monitoring blood plasma pH may provide some indication of the severity of certain illnesses or medical conditions. Conventional electrodes used for monitoring intra-arterial or intra-venous blood plasma pH generally include glass or antimony electrodes. A typical glass electrode consists of a glass bulb, which encloses a metal electrode immersed within an electrolytic solution. Unfortunately, conventional glass electrodes suffer from many disadvantages. For example, glass electrodes are often extremely fragile, and therefore, undesirably expensive to produce and transport. Due to their relatively high electrical impedance, glass electrodes also demonstrate a prolonged time response and require heavily shielded probe leads to reduce unwanted noise components in the probe signal. In addition, the inherent rigidity of glass electrodes does not allow for minimization of patient discomfort when measuring in vivo pH levels.
As yet another disadvantage, most glass electrodes require the use of an external reference electrode, which as described below, is undesirable for several reasons. Recently, combination pH and reference electrodes have been fabricated within a single glass enclosure. However, the present inventors are unaware of a commercially available combination pH and reference glass electrode having a size substantially less than 1.0 mm in diameter.
In an effort to overcome the disadvantages of glass electrodes, antimony electrodes have been constructed for use in monitoring in vitro and in vivo pH levels. As one advantage, antimony electrodes can be made much smaller and more robust than pH electrodes made from glass. In addition, the antimony electrode is a relatively low impedance device (e.g., 1 MΩ or less) compared to the glass electrode (e.g., 12 MΩ). As such, antimony electrodes demonstrate shorter time responses than glass electrodes and do not require shielding, in most cases.
However, conventional antimony electrodes suffer from their own disadvantages. In one example, a method of constructing an antimony electrode includes forming an antimony rod from which relatively small fragments are cut or otherwise detached from the rod. After attaching one of the fragments to a wire lead, the assembly is encased within a glass tube leaving an upper portion of the antimony fragment exposed for sensing purposes. Unfortunately, antimony electrodes formed in such a manner suffer from the effects of a rough sensing surface; namely, undesirable fluctuations in pH measurements.
In an effort to reduce signal fluctuations, another method has been disclosed in which an antimony fragment and attached wire lead are completely coated in a hard-setting acrylic resin. By grinding one end of the resin-coated electrode to produce a substantially flat planar surface, a portion of the antimony fragment is exposed for sensing purposes. Unfortunately, the grinding action tends to pull the exposed antimony portion away from the acrylic resin coating, resulting in the formation of micro-crevices between the exposed antimony portion and the acrylic resin coating. In some cases, fluids may become trapped within these micro-crevices, resulting in sample contamination and erroneous pH measurements when the electrode is transferred to another position. In addition, fluctuations in pH measurements may still occur if the exposed antimony portion does not exhibit a completely smooth sensing surface.
In addition to inconsistent and erratic pH measurements, the above-mentioned antimony electrodes suffer from several other disadvantages. As noted above, conventional antimony electrodes are typically encased within inflexible materials, such as glass tubes or hard-setting resins. These inflexible materials are not conducive to minimizing patient discomfort when measuring in vivo pH levels. In addition, the above-mentioned antimony electrodes require the use of external reference and temperature electrodes; the disadvantages of which will be described in more detail below.
pH-sensitive electrodes, such as the glass and antimony electrodes described above, are configured to provide an electrical potential that is sensitive to changes in hydrogen ion concentration. However, pH-sensitive electrodes must be combined with reference electrodes, which are configured to provide a constant electrical potential independent of hydrogen ion concentration, to determine the pH of a sample medium. In this manner, the pH may be determined by the “electrode potential difference,” or the difference in electrical potentials measured by the pH-sensitive electrode (i.e., the active electrode) and the reference electrode.
As noted above, most conventional pH-sensitive electrodes are used in combination with external reference electrodes, which are coupled to the sample medium at a location spaced apart from the active electrode. Examples of conventional external reference electrodes include skin surface electrodes (e.g., a standard EKG electrode) and separate needle electrodes, which may be placed in the vicinity of the sample medium or simply within the patient's body (e.g., within any subcutaneous tissue). As another example, reference half-cells have also been combined with conventional pH-sensitive electrodes. In general, a reference half-cell is an external reference electrode, which is electrochemically coupled to the sample medium via a salt bridge, and typically includes a metal-chloride electrode (e.g., a calomel (Hg:HgCl) or Ag:AgCl electrode) immersed within an electrolyte. Unfortunately, due to the inevitable distance separating the active and reference electrodes, a decrease in accuracy and an increase in time response can be attributed to all external reference electrodes.
Due to the influence of temperature on antimony, pH measurements obtained with antimony electrodes are often offset, and thus, require temperature compensation to obtain “true” pH measurements. Previous attempts at temperature compensation include obtaining and manually entering a patient's body temperature into an analytical device. Alternatively, an external temperature electrode may be used to detect the temperature of an area somewhat removed from the antimony electrode. Unfortunately, such methods are often inconvenient and sometimes inaccurate (e.g., when the measured temperature differs from the temperature at the pH measurement site).
Therefore, a need exists for a pH-sensitive electrode that overcomes the disadvantages described above, and more specifically, for a combination pH probe having an antimony electrode, a reference electrode and a temperature electrode formed within a single probe housing. Such a combination pH probe would provide stable and accurate pH measurements, while demonstrating a time response, which is significantly faster than the time response of conventional electrodes. Preferably, the combination pH probe would provide a minimally invasive means for obtaining quick and accurate pH measurements within in vivo or in vitro samples of physiological fluids, such as blood plasma, gastric secretions, pancreatic secretions, saliva, and other bodily fluids.
In addition to physiological fluids, the combination probe would also provide a minimally invasive means for obtaining in vivo pH measurements of interstitial fluids within physiological tissues and muscles. As noted above, conventional electrodes are often used for monitoring changes in intra-arterial or intra-venous blood plasma pH. Due to the compensatory effects of buffering in the blood, however, such monitoring provides an undesirably late indication of underlying problems, which manifest originally within the affected tissues and muscles. Unfortunately, detecting a change in the blood plasma pH indicates that irreversible damage to the tissue cells has already occurred.
Recently, a few electrodes have been described as able to monitor pH levels within human or animal tissues, muscles and organs. Due to their relatively large size, however, these electrodes inevitably cause at least some amount of local tissue damage. In some cases, insertion of an electrode greater than 1.0 mm in diameter may inflict enough local tissue damage to cause intracellular release of substantial amounts of hydrogen ions, resulting in local ischemia and underestimated pH measurements.
Clearly, a need remains for a combination pH probe having pH-, reference-, and temperature-sensing capabilities formed within a probe housing, which is small enough for obtaining in vivo pH measurements within tissues and muscles without inflicting significant local tissue damage.